Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination
Abstract
Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.
Data availability
The sequencing data that support the findings of this study have been deposited on Zenodo (https://doi.org/10.5281/zenodo.3989144).
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Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon vaccinationzenodo - 10.5281/zenodo.3989144.
Article and author information
Author details
Funding
University of Antwerp
- George Elias
- Esther Bartholomeus
- Nicolas De Neuter
Research Foundation Flanders
- Pieter Meysman
- Kris Laukens
- Benson Ogunjimi
American Lebanese Syrian Associated Charities
- Aisha Souquette
- Paul G Thomas
National Institute of Allergy and Infectious Diseases
- Aisha Souquette
- Paul G Thomas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Protocols involving the use of human tissues were approved by the Ethics Committee of Antwerp University Hospital and University of Antwerp (Antwerp, Belgium), and all of the experiments were performed in accordance with the protocols
Reviewing Editor
- Armita Nourmohammad, University of Washington, United States
Version history
- Preprint posted: August 25, 2020 (view preprint)
- Received: March 14, 2021
- Accepted: January 7, 2022
- Accepted Manuscript published: January 25, 2022 (version 1)
- Accepted Manuscript updated: January 26, 2022 (version 2)
- Version of Record published: February 8, 2022 (version 3)
Copyright
© 2022, Elias et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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